The Effect of Sequential Therapy on Alzheimer's Disease

August 17, 2026 updated by: Jinzhou Tian, Dongzhimen Hospital, Beijing

The Effect of Sequential Therapy on Alzheimer's Disease: A Prospective Cohort Study

The goal of this observational study is to learn how Alzheimer's disease changes over time in people at different stages of the disease. It will look at changes in memory and thinking, daily activities, behavior, and traditional Chinese medicine symptom patterns. It will also learn about the outcomes and safety of sequential traditional Chinese medicine treatment based on the stage of Alzheimer's disease. The main questions this study aims to answer are:

  • How do memory and thinking, daily activities, behavior, and traditional Chinese medicine symptom patterns naturally change over time in participants with early-, middle-, and late-stage Alzheimer's disease?
  • How do symptoms and traditional Chinese medicine symptom patterns change together as Alzheimer's disease progresses?
  • Do participants receiving stage-based sequential traditional Chinese medicine treatment have different changes in memory and thinking, daily activities, behavior, and overall disease status?
  • What medical problems or side effects occur during sequential traditional Chinese medicine treatment?

About 600 participants aged 55 to 85 years will take part in this study. Participants will be followed for 12 months.

Participants will:

  • Visit the study center at the start of the study and at 3, 6, 9, and 12 months.
  • Complete assessments of memory and thinking, daily activities, behavior, overall disease status, and traditional Chinese medicine symptoms.
  • Have blood tests and other study examinations.
  • Have their treatment use and medical problems recorded during follow-up.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Alzheimer's disease has a progressive clinical course, and traditional Chinese medicine theory describes changes in syndrome patterns across different stages of the disease. In the early stage, kidney deficiency is considered the predominant pattern. In the middle stage, phlegm, fire, and blood stasis may become more prominent, while the late stage is characterized by severe qi deficiency. Based on this stage-related evolution, a sequential traditional Chinese medicine approach was developed according to the "syndrome cascade hypothesis." Preliminary clinical observations have suggested potential benefits for cognitive function and overall clinical status, but evidence from prospective multicenter studies remains limited.

This prospective multicenter cohort study has three main objectives. First, it will describe the natural changes in cognitive function, activities of daily living, neuropsychiatric symptoms, and traditional Chinese medicine syndrome patterns across the early, middle, and late stages of Alzheimer's disease. It will also characterize the dynamic relationship between clinical symptoms and traditional Chinese medicine syndrome patterns during disease progression. Second, it will evaluate the clinical outcomes associated with stage-based sequential traditional Chinese medicine therapy, including short- and long-term clinical changes. Third, it will evaluate the safety of sequential traditional Chinese medicine therapy in real-world clinical use.

Treatment exposure will be recorded prospectively. Exposure assessment will consider cumulative medication use, medication adherence, treatment continuity, and treatment interruption. Information from medication dispensing and return records, medication diaries, and investigator follow-up records will be used to assess treatment exposure. The time from the beginning of treatment exposure to subsequent outcome assessment will also be recorded.

General demographic and baseline clinical characteristics will be summarized using descriptive statistics. Continuous outcomes will be analyzed using linear mixed-effects models to evaluate changes over time. The models will include time, exposure status, and the interaction between time and exposure status. Single-time-point comparisons may use independent-samples tests or analysis of covariance, as appropriate. Binary outcomes will be analyzed using logistic regression, with adjustment for potential confounding factors when appropriate.

Prespecified subgroup analyses will explore whether the associations with sequential therapy differ according to disease stage, age, sex, baseline cognitive function, concomitant use of Western medicines, and traditional Chinese medicine syndrome type. Interaction terms between subgroup factors and exposure status will be used to explore differences among subgroups. These subgroup analyses will be considered exploratory.

Missing data patterns will be assessed to determine whether data are missing completely at random, missing at random, or missing not at random. Multiple imputation will be used for missing primary outcomes and key covariates, with variables related to missingness included in the imputation model. Sensitivity analyses will be performed to examine the robustness of the findings under different assumptions and exposure definitions.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
600

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100700
        • Recruiting
        • Dongzhimen Hospital, Beijing University of Chinese Medicine
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The study population consists of participants with different stages of Alzheimer's disease recruited from Dongzhimen Hospital, Beijing University of Chinese Medicine, and participating study centers. Recruitment settings include brain disease departments, neurology departments, memory clinics, and traditional Chinese medicine outpatient clinics. Participants include individuals with mild cognitive impairment due to Alzheimer's disease and those with mild, moderate, or severe Alzheimer's dementia.

Description

Inclusion Criteria:

  • Age 55 to 85 years, regardless of sex.
  • Memory decline reported by the participant or family member for at least 6 months.
  • Meets the diagnostic criteria for the target disease and is clinically diagnosed with mild cognitive impairment due to Alzheimer's disease or mild, moderate, or severe Alzheimer's dementia.
  • Able to complete clinical scale assessments and blood sampling.
  • Able to undergo brain magnetic resonance imaging (MRI) or amyloid-beta positron emission tomography (Aβ-PET) examinations using the tracers specified in the study protocol.
  • Written informed consent provided by the participant or a legally authorized representative.
  • Able to complete study follow-up.
  • Participants with a known allergy to components of the exposure medications will be assigned to the non-exposed group.

Exclusion Criteria:

  • Cerebrovascular disease, traumatic brain injury, thyroid dysfunction, vitamin deficiency, or other diseases sufficient to cause cognitive impairment.
  • Malignant tumors unrelated to the target disease, hematological diseases, severe psychiatric disorders, depression, or anxiety disorders.
  • Severe dysfunction of major organs, including the heart, brain, liver, or kidneys.
  • Infectious diseases, including HIV or HBV infection.
  • Pregnancy, breastfeeding, or plans for pregnancy in the near future.
  • Gastrointestinal diseases that may affect drug absorption.
  • Use of medications affecting cognitive function within 4 weeks before enrollment.
  • Recent participation in or current participation in another trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Early-Stage AD With Kidney-Tonifying Formula

Participants with early-stage Alzheimer's disease who receive the Kidney-Tonifying Formula and meet the prespecified exposure criteria.

Kidney-Tonifying Formula：Qinggong Shoutao Pills (Daren Tang) contain donkey kidney, deer kidney, dog kidney, ginseng, Tian Dong, Mai Dong, goji berry, Rehmannia root, Dang Gui, salt-processed Yi Zhi, stir-fried Suan Zao Ren, charred Fen Xin Mu, and other ingredients. The prescribed dose is 50 pills (7 g) orally twice daily.
Middle-Stage AD With Kidney-Tonifying and Phlegm-Resolving Formula

Participants with middle-stage Alzheimer's disease who receive the Kidney-Tonifying and Phlegm-Resolving Formula and meet the prespecified exposure criteria.

Kidney-Tonifying and Phlegm-Resolving Formula：Modified Huanshaodan consists of prepared Rehmannia root 10 g, Chinese yam 10 g, Niu Xi 9 g, goji berry 10 g, Shan Zhu Yu 10 g, Poria 15 g, Du Zhong 10 g, processed Yuan Zhi 9 g, Wu Wei Zi 10 g, Shi Chang Pu 3 g, Ba Ji Tian 10 g, Cistanche tubulosa 10 g, ginseng 9 g, and Yu Jin (Guangxi E Zhu) 9 g. One packet is taken orally twice daily.
Late-Stage AD With Kidney-Tonifying and Collapse-Preventing Formula

Participants with late-stage Alzheimer's disease who receive the Kidney-Tonifying and Collapse-Preventing Formula and meet the prespecified exposure criteria.

Kidney-Tonifying and Collapse-Preventing Formula：Modified Yiwang Shuangquandan consists of ginseng 9 g, Qian Shi 15 g, Chinese yam 10 g, Mai Dong 10 g, Wu Wei Zi 10 g, Suan Zao Ren 10 g, Yuan Zhi 6 g, Shi Chang Pu 3 g, Dang Gui 10 g, Sang Piao Xiao 5 g, prepared Rehmannia root 10 g, Shan Zhu Yu 10 g, Huang Qi 5 g, Huang Lian 3 g, Mu Dan Pi 10 g, and Tu Si Zi 10 g. One packet is taken orally twice daily.
Non-Exposed Group
Participants who do not receive the study medication, have medication adherence below 80%, discontinue treatment during follow-up, or do not complete the prespecified follow-up period are classified as the non-exposed group.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB)
Time Frame: Baseline to Month 12
The Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) is used to assess overall cognitive and functional impairment. The total score ranges from 0 to 18, with higher scores indicating greater disease severity and a worse outcome. The outcome is the change in CDR-SB score from baseline to Month 12.
Baseline to Month 12
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog11)
Time Frame: Baseline to Month 12
The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is used to assess cognitive impairment in participants with early- and middle-stage Alzheimer's disease. The standard 11-item ADAS-Cog total score ranges from 0 to 70, with higher scores indicating greater cognitive impairment and a worse outcome. The outcome is the change in ADAS-Cog score from baseline to Month 12.
Baseline to Month 12
Change From Baseline in Severe Impairment Battery (SIB)
Time Frame: Baseline to Month 12
The Severe Impairment Battery (SIB) is used to assess cognitive function in participants with late-stage Alzheimer's disease. The total score ranges from 0 to 100, with higher scores indicating better cognitive function and a better outcome. The outcome is the change in SIB score from baseline to Month 12.
Baseline to Month 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Mini-Mental State Examination (MMSE)
Time Frame: Baseline to Month 12
The Mini-Mental State Examination (MMSE) is used to assess cognitive function. The total score ranges from 0 to 30, with higher scores indicating better cognitive function and a better outcome. The outcome is the change in MMSE score from baseline to Month 12.
Baseline to Month 12
Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)
Time Frame: Baseline to Month 12
The Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) is used to assess performance of activities of daily living. The total score ranges from 0 to 78, with higher scores indicating greater independence in daily functioning and a better outcome. The outcome is the change in ADCS-ADL score from baseline to Month 12.
Baseline to Month 12
Change From Baseline in Neuropsychiatric Inventory (NPI)
Time Frame: Baseline to Month 12
The Neuropsychiatric Inventory (NPI) is used to assess neuropsychiatric symptoms. The 12-domain total score ranges from 0 to 144, with higher scores indicating more severe neuropsychiatric symptoms and a worse outcome. The outcome is the change in NPI score from baseline to Month 12.
Baseline to Month 12
Change From Baseline in Blood Aβ42/Aβ40 Ratio
Time Frame: Baseline to Month 12
The blood amyloid beta 42 to amyloid beta 40 (Aβ42/Aβ40) ratio will be measured at baseline and Month 12. The Aβ42/Aβ40 ratio is a dimensionless value. The outcome is the change in the Aβ42/Aβ40 ratio from baseline to Month 12.
Baseline to Month 12
Change From Baseline in Blood Phosphorylated Tau 181 (P-Tau181)
Time Frame: Baseline to Month 12
Blood phosphorylated tau 181 (P-Tau181) will be measured in picograms per milliliter (pg/mL) at baseline and Month 12. The outcome is the change in P-Tau181 concentration from baseline to Month 12.
Baseline to Month 12
Change From Baseline in Blood Phosphorylated Tau 217 (P-Tau217)
Time Frame: Baseline to Month 12
Blood phosphorylated tau 217 (P-Tau217) will be measured in picograms per milliliter (pg/mL) at baseline and Month 12. The outcome is the change in P-Tau217 concentration from baseline to Month 12.
Baseline to Month 12
Change From Baseline in Blood Neurofilament Light Chain (NfL)
Time Frame: Baseline to Month 12
Blood neurofilament light chain (NfL) will be measured in picograms per milliliter (pg/mL) at baseline and Month 12. The outcome is the change in NfL concentration from baseline to Month 12.
Baseline to Month 12
Change From Baseline in Blood Glial Fibrillary Acidic Protein (GFAP)
Time Frame: Baseline to Month 12
Blood glial fibrillary acidic protein (GFAP) will be measured in picograms per milliliter (pg/mL) at baseline and Month 12. The outcome is the change in GFAP concentration from baseline to Month 12.
Baseline to Month 12

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence of Serious Adverse Events
Time Frame: Up to 12 months
The number and proportion of participants experiencing serious adverse events during the study follow-up period.
Up to 12 months
Incidence of Adverse Events
Time Frame: Up to 12 months
The number and proportion of participants experiencing adverse events during traditional Chinese medicine use and follow-up. Adverse events include any unfavorable medical events occurring during treatment or follow-up, including symptoms, signs, or laboratory abnormalities, regardless of whether they are considered related to treatment.
Up to 12 months
Change From Baseline in Kidney Deficiency Score Assessed by the Revised Pattern Elements Scale in Alzheimer's Disease （PES-AD）
Time Frame: Baseline and Months 3, 6, 9, and 12
Kidney deficiency is assessed using the kidney deficiency subscale of the Revised Pattern Elements Scale in Alzheimer's Disease (PES-AD). The score ranges from 0 to 21, with higher scores indicating a greater degree of kidney deficiency and therefore a worse pattern outcome. A score of 7 or higher indicates the presence of the kidney deficiency pattern element. The outcome is the change from baseline in the kidney deficiency score at each follow-up assessment.
Baseline and Months 3, 6, 9, and 12
Change From Baseline in Phlegm Obstruction Score Assessed by the Revised Pattern Elements Scale in Alzheimer's Disease (PES-AD)
Time Frame: Baseline and Months 3, 6, 9, and 12
Phlegm obstruction is assessed using the phlegm obstruction subscale of the Revised Pattern Elements Scale in Alzheimer's Disease (PES-AD). The score ranges from 0 to 20, with higher scores indicating a greater degree of phlegm obstruction and therefore a worse pattern outcome. A score of 7 or higher indicates the presence of the phlegm obstruction pattern element. The outcome is the change from baseline in the phlegm obstruction score at each follow-up assessment.
Baseline and Months 3, 6, 9, and 12
Change From Baseline in Fire Disturbance Score Assessed by the Revised Pattern Elements Scale in Alzheimer's Disease (PES-AD)
Time Frame: Baseline and Months 3, 6, 9, and 12
Fire disturbance is assessed using the fire disturbance subscale of the Revised Pattern Elements Scale in Alzheimer's Disease (PES-AD). The score ranges from 0 to 20, with higher scores indicating a greater degree of fire disturbance and therefore a worse pattern outcome. A score of 7 or higher indicates the presence of the fire disturbance pattern element. The outcome is the change from baseline in the fire disturbance score at each follow-up assessment.
Baseline and Months 3, 6, 9, and 12
Change From Baseline in Blood Stasis Score Assessed by the Revised Pattern Elements Scale in Alzheimer's Disease (PES-AD)
Time Frame: Baseline and Months 3, 6, 9, and 12
Blood stasis is assessed using the blood stasis subscale of the Revised Pattern Elements Scale in Alzheimer's Disease (PES-AD). The score ranges from 0 to 20, with higher scores indicating a greater degree of blood stasis and therefore a worse pattern outcome. A score of 7 or higher indicates the presence of the blood stasis pattern element. The outcome is the change from baseline in the blood stasis score at each follow-up assessment.
Baseline and Months 3, 6, 9, and 12
Change From Baseline in Yang Deficiency Score Assessed by the Revised Pattern Elements Scale in Alzheimer's Disease (PES-AD)
Time Frame: Baseline and Months 3, 6, 9, and 12
Yang deficiency is assessed using the Yang deficiency subscale of the Revised Pattern Elements Scale in Alzheimer's Disease (PES-AD). The score ranges from 0 to 21, with higher scores indicating a greater degree of Yang deficiency and therefore a worse pattern outcome. A score of 7 or higher indicates the presence of the Yang deficiency pattern element. The outcome is the change from baseline in the Yang deficiency score at each follow-up assessment.
Baseline and Months 3, 6, 9, and 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Dongzhimen Hospital, Beijing

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: JinZhou Tian, Dongzhimen Hospital, Beijing

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 30, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 12, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 12, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 17, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 19, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 17, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DXMG-JBZX-25001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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